The Applicant Company has already proposed a solution to this problem of progesterone degradation in patent application FR 76 36007. The Company has developed a formulation of capsules containing progesterone in an oily suspension which ensures good protection of the active constituent against its degradation by the liver.
The process for manufacturing such capsules has however proven to be both complex and costly to implement, and requires considerable know-how. Attempts have therefore been made to develop efficient and also economically viable alternative formulations.
Accordingly, in European patent no. 0 335 907, the PHARMAGYN Company describes tablets containing micronized progesterone in association with a wax, both in powdery form. It is pointed out in this patent that inclusion of large quantities of wax in the tablets enables to limit the degradation of progesterone by the liver, thereby increasing its bio-availability.
Similarly, in international patent application WO95/05807 the NOVO NORDISK Company describes tablets containing progesterone and a polyethylene glycol, as well as an excipient chosen from the group containing starches, starch-containing components, modified starches, celluloses, modified celluloses, pectins and tragacanth. It is pointed out in this document that the presence of polyethylene glycol and of the excipient in the tablets results in a favourable effect on the bio-availability of orally administered progesterone.
It should be stressed that the tablets described in these two documents contain high percentages of excipients. Tablets made according to the examples given in patent EP 0 335 970 contain 68% excipients, while those in the patent application WO 95/05807 contain about 49% to 62% excipients.
It is known that excipients in tablets play various roles. They are used to increase the stability of the active constituents, to obtain a particular release profile according to the nature of the excipient, but they are mainly used to facilitate compression of the various ingredients in order to obtain a tablet having the desired properties of hardness, disintegration and dissolution.